This research has centered around interrelationships between cholecystokinin-containing neurons and opioid peptide-containing neurons in brain and spinal cord. More precisely it represents the prelude to studying the relationship. At present, we are in the process of quantitating (via specific radioimmunoassay), localizing (via immunocytochemistry) and characterizing (via HPLC and gel filtration) these peptides in various systems. One system of particular interest is the mesolimbic dopamine system in which CCK coexists with dopamine. These neurons may interact with enkephalin and dynorphin neurons in nucleus accumbens - olfactory tubercle and possibly in striatum. These studies are of particular relevance to schizophrenia in which a disorder of dopamine transmission is hypothesized especially in the limbic and cortical projections which also contain CCK. In spinal cord CCK may act to influence our preception of tactile and thermal stimuli especially painful stimuli. CCK also acts to antagonize morphine analgesia. We are presently characterizing opiate peptides in cord representative of the pro-enkephalin A and B families (e.g. dynorphin 1-17, dynorphin 1-8, met5-enkephalin, met5-enkephalin-arg6-phe7 and met5-enkephalin-arg6-gly7-leu8) as well as CCK. The studies on spinal cord are important to our understanding of pain, its pathways, the neurotransmitters involved, and the possibility of modulating morphine tolerance in chronic pain situations such as cancer. Lastly, we are in the initial stages of cloning the CCK mRNA in order to elucidate the structure of the CCK precursor molecule. This research will provide us with a new tool, called a cDNA probe, to investigate the regulation of CCK in brain by drugs, other transmitter systems, and behavioral manipulations. We hope also that this information will be useful to researchers and clinician working in gastroenterology, a field in which CCK is also very important. It seems likely that CCK not only helps us digest our food but helps us digest our thoughts as well!